Formation of amyloid in encapsulated human pancreatic and human stem cell-generated beta cell implants.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Freya Van HulleDaniel Pipeleers

Abstract

Detection of amyloid in intraportal islet implants of type 1 diabetes patients has been proposed as cause in their functional decline. The present study uses cultured adult human islets devoid of amyloid to examine conditions of its formation. After intraportal injection in patients, amyloid deposits <15 µm diameter were identified in 5%-12% of beta cell containing aggregates, 3-76 months posttransplant. Such deposits also formed in glucose-controlling islet implants in the kidney of diabetic mice but not in failing implants. Alginate-encapsulated islets formed amyloid during culture when functional, and in all intraperitoneal implants that corrected diabetes in mice, exhibiting larger sizes than in functioning nonencapsulated implants. After intraperitoneal injection in a patient, retrieved single capsules presented amyloid near living beta cells, whereas no amyloid occurred in clustered capsules with dead cells. Amyloid was also demonstrated in functional human stem cell-generated beta cell implants in subcutaneous devices of mice. Deposits up to 35 µm diameter were localized in beta cell-enriched regions and related to an elevated IAPP over insulin ratio in the newly generated beta cells. Amyloid in device-encapsulated human...Continue Reading

References

Aug 24, 1989·The New England Journal of Medicine·K H JohnsonP Westermark
Nov 14, 1986·Biochemical and Biophysical Research Communications·P WestermarkK Sletten
Jan 1, 1972·Upsala Journal of Medical Sciences·P Westermark
May 1, 1995·Diabetologia·P WestermarkA Andersson
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·C B VerchereS E Kahn
Feb 26, 1999·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·E J de KoningA Clark
Aug 10, 2000·The New England Journal of Medicine·J W HöppenerC J Lips
Mar 6, 2004·Upsala Journal of Medical Sciences·Gunilla T WestermarkArne Andersson
Aug 5, 2004·The Journal of Clinical Endocrinology and Metabolism·Rebecca L HullSteven E Kahn
Sep 29, 2006·The New England Journal of Medicine·A M James ShapiroJonathan R T Lakey
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bart KeymeulenDaniel Pipeleers
Aug 30, 2008·The New England Journal of Medicine·Gunilla T WestermarkUNKNOWN Nordic Network for Clinical Islet Transplantation
Oct 18, 2008·Diabetes, Obesity & Metabolism·D PipeleersF Gorus
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Rodolfo Guardado-MendozaFranco Folli
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·K J PotterC B Verchere
Jun 7, 2011·The American Journal of Pathology·Catherine A JurgensRebecca L Hull
Jul 12, 2011·Physiological Reviews·Per WestermarkGunilla T Westermark
Dec 24, 2011·Transplantation·Gunilla T WestermarkPer Westermark
May 17, 2012·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Sara Bohman, Gunilla T Westermark
Sep 7, 2012·Diabetes, Obesity & Metabolism·J MontaneC Bruce Verchere
Jul 19, 2014·The Journal of Clinical Investigation·Dhananjay Gupta, Jack L Leahy
Sep 11, 2014·American Journal of Physiology. Endocrinology and Metabolism·Evi MottéDaniel Pipeleers
Apr 3, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K J PotterC B Verchere
Apr 4, 2017·The Journal of Clinical Endocrinology and Metabolism·Jaques A CourtadeC Bruce Verchere
Aug 3, 2017·The Journal of Experimental Medicine·Abhisek MukherjeeClaudio Soto
Aug 18, 2017·Upsala Journal of Medical Sciences·Gunilla T WestermarkJohnny Ludvigsson
Dec 31, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Per-Ola CarlssonOlle Korsgren

❮ Previous
Next ❯

Citations

Jun 25, 2021·Frontiers in Immunology·Anna TorunBeata Pyrzynska

❮ Previous
Next ❯

Related Concepts

Related Feeds